System and method for determining dosimetry in ophthalmic photomedicine

ABSTRACT

A system and method for treating ophthalmic target tissue, including a light source for generating a beam of light, a beam delivery system that includes a scanner for generating patterns, and a controller for controlling the light source and delivery system to create a dosimetry pattern of the light beam on the ophthalmic target tissue. One or more dosage parameters of the light beam vary within the dosimetry pattern, to create varying exposures on the target tissue. A visualization device observes lesions formed on the ophthalmic target tissue by the dosimetry pattern. The controller selects dosage parameters for the treatment beam based upon the lesions resulting from the dosimetry pattern, either automatically or in response to user input, so that a desired clinical effect is achieved by selecting the character of the lesions as determined by the dosimetry pattern lesions.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application is a divisional of U.S. Non-provisional applicationSer. No. 13/691,691, filed Nov. 30, 2012, which is a continuation ofU.S. Non-provisional application Ser. No. 11/939,398, filed Nov. 13,2007, now U.S. Pat. No. 8,336,555, which claims the benefit of U.S.Provisional Application No. 60/857,951, filed Nov. 10, 2006. The contentof the above-referenced applications is incorporated herein by referencefor all purposes.

FIELD OF THE INVENTION

A system and method for determining dosimetry for photothermal treatmentof ocular structures, for example, the retinal pigmented epithelium,photoreceptors, and other retinal layers, and those of the trabecularmeshwork. It is particularly useful in the treatment of a variety ofretinal disorders, as well as ocular hypertension.

BACKGROUND OF THE INVENTION

Laser photomedicine is a well-established therapeutic modality for awide variety of conditions. To date, the use of ophthalmic lasers hasbeen limited to either short (around one microsecond or shorter) pulsesystems for sub-cellular targeting, or long (hundreds of microsecondsand longer) pulse systems that indiscriminately denature relativelylarge volumes of tissue.

For example, present standard retinal photocoagulative treatment forconditions such as Diabetic Retinopathy, and Age-Related MacularDegeneration utilize visible laser light with exposure durations on theorder of 100 ms. Generation of heat due to absorption of visible laserlight occurs predominantly in the retinal pigmented epithelium (RPE) andpigmented choriocappilaris, the melanin containing layers directlybeneath the photoreceptors of the sensory retina. The RPE is disposedbetween the sensory retina and the choroid. Due to heat diffusion duringlong exposures, this standard therapy also irreversibly damages theoverlying sensory retina.

Although it does halt the progress of the underlying disease, suchirreversible damage decreases the patient's vision by destroying notonly the photoreceptors in the irradiated portion of the retina but alsoby creating permanent micro-scotomas, and possibly also damaging theretinal nerve fibers that traverse the targeted portion of the retina,creating a defect called arc scotoma. Such nerve fiber damage eliminatesthe signals it would have carried from distal areas of the retina, thusunnecessarily further worsening the patient's vision.

To address these issues, systems and methods for creating spatiallyconfined photothermal lesions in ocular tissues have been proposed, suchas in co-pending U.S. patent application Ser. No. 11/606,451, which isincorporated herein by reference. However, what is lacking in suchsystems and methods is a means for gauging a patient's idiosyncraticresponse and for reliable delivery of the treatment light to createlesions in response thereto.

Due to strong variability of the retinal absorption, ocular transmissionof light, and choroidal blood perfusion, the laser-induced retinaltemperature rise strongly varies from patient to patient, and even fromlocation to location in a single patient. So, a global parameter settingfor a desired clinical result is not ideal. Left uncorrected, thesedifferences can lead to inhomogeneous treatments, over-treating in someareas and under-treating in others. Physicians have traditionallydetermined the appropriate treatment for each patient (and even fordifferent areas in the retina of the same patient) by a “trial anderror” approach, which takes a significant amount of time and isentirely qualitative.

Accordingly, there is a need for a rapid, robust, and cost-effectivesystem and method for providing predictable ophthalmic photomedicaltreatment such as, but not limited to, the retina and trabecularmeshwork, that is not provided by known methods or devices.

SUMMARY OF THE INVENTION

The present invention solves the aforementioned problems by providing asystem and method for treating ophthalmic target tissue using a“dosimetry pattern” of light of varying pulse durations, spot sizesand/or power densities to efficiently determine the photothermal targetproperties, and provide more predictable treatment results. Thedosimetry pattern may be a plurality of fixed spots, one or morecontinuous scans resulting in one or more straight or curved linesegments, or a combination of both. By locating the region within thedosimetry pattern that provides a visible lesion of a desirablecharacter, or extrapolating such a region, the operating physician maythen choose the appropriate system parameters for a given treatment.Alternately, the photomedical system may incorporate an imaging systemthat identifies the lesions within the dosimetry pattern with thedesired clinical results, and adjusts the system parameters in anautomated fashion.

A system for treating ophthalmic target tissue includes a light sourcefor generating a beam of light, a beam delivery unit for delivering thebeam of light to ophthalmic target tissue, wherein the beam deliveryunit includes a scanner unit for deflecting the beam of light, acontroller for controlling at least one of the light source and the beamdelivery unit to create a dosimetry pattern of the beam of light on theophthalmic target tissue for which at least one dosage parameter of thebeam of light varies within the dosimetry pattern, and a visualizationdevice for capturing an image of lesions formed on the ophthalmic targettissue by the dosimetry pattern. The controller is configured to controlat least one of the light source and the beam delivery unit to thendeliver the beam of light to the ophthalmic target tissue having atleast one dosage parameter thereof selected in response to the capturedimage of lesions.

A method of treating ophthalmic target tissue includes generating a beamof light, delivering the beam of light to ophthalmic target tissue usinga scanner unit for deflecting the beam of light, creating a dosimetrypattern of the beam of light on the ophthalmic target tissue for whichat least one dosage parameter of the beam of light varies within thedosimetry pattern, capturing an image of lesions formed on theophthalmic target tissue by the dosimetry pattern, selecting at leastone dosage parameter for the beam of light in response to the capturedimage of lesions, and delivering the beam of light to the ophthalmictarget tissue having the selected at least one dosage parameter.

In another aspect, a system for treating ophthalmic target tissueincludes a light source for generating a beam of light, a beam deliveryunit for delivering the beam of light to ophthalmic target tissue,wherein the beam delivery unit includes a scanner unit for deflectingthe beam of light, a controller for controlling at least one of thelight source and the beam delivery unit to create a dosimetry pattern ofthe beam of light on the ophthalmic target tissue for which at least onedosage parameter of the beam of light varies within the dosimetrypattern, a visualization apparatus for observing lesions formed on theophthalmic target tissue by the dosimetry pattern, and a user interfacefor receiving information about the observed lesions. The controller isconfigured to control at least one of the light source and the beamdelivery unit to then deliver the beam of light to the ophthalmic targettissue having at least one dosage parameter thereof selected in responseto the received information.

In yet one more aspect, a method for treating ophthalmic target tissueincludes generating a beam of light using a light source, delivering thebeam of light to ophthalmic target tissue using a beam delivery unithaving a scanner unit for deflecting the beam of light, creating adosimetry pattern of the beam of light on the ophthalmic target tissuefor which at least one dosage parameter of the beam of light varieswithin the dosimetry pattern, observing lesions formed on the ophthalmictarget tissue by the dosimetry pattern, entering information about theobserved lesions using a user interface that is connected to acontroller that controls at least one of the light source and the beamdelivery unit, selecting at least one dosage parameter for the beam oflight in response to the entered information, and controlling at leastone of the light source and the beam delivery unit using the controllerto then deliver the beam of light to the ophthalmic target tissue havingthe at least one selected dosage parameter.

Other objects and features of the present invention will become apparentby a review of the specification, claims and appended figures.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic diagram illustrating a system for retinaltreatment.

FIG. 2 is a schematic diagram illustrating an alternate embodiment ofthe system of FIG. 1, specifically for trabecular meshwork treatment.

FIG. 3 is a schematic diagram illustrating an embodiment of thedosimetry pattern formed by discrete pulses.

FIG. 4 is a schematic diagram illustrating an alternate embodiment ofthe dosimetry pattern formed by a continuous scan.

FIG. 5 is a system GUI display indicator that indicates the character ofthe lesion based upon the results of the dosimetry pattern and selectedpulse parameters.

FIG. 6 is an alternate embodiment of the system GUI display indicator,based upon the ongoing results of the treatment.

FIG. 7 is an alternate embodiment of the system GUI display indicatorfor selecting the spatial selectivity of the lesion, based upon theresults of the dosimetry pattern.

FIG. 8 is a schematic diagram showing the use of visible fiduciallesions to indicate the boundary of a pattern of ophthalmoscopicallyinvisible lesions.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention is a system and method for the efficientdetermination of treatment parameters needed to form desired ophthalmicphotothermal lesions, which allows for the proper setting and adjustmentof the treatment parameters. The system operates based on the visibleresponse of the target tissue to a dosimetry pattern of light whichcreates lesions on the target tissue. Tissue appearance following itsexposure to the dosimetry pattern helps the system and/or user to selectappropriate system settings for subsequent treatment. A specific lesionexhibiting the character to produce the desired clinical effect may beidentified and corresponding system settings used, or the settings maybe extrapolated from the observation of the results of the dosimetrypattern.

FIG. 1 illustrates a system 1 for implementing ophthalmic photothermaltreatment, which includes a control unit 10, a light generation unit 12and a light delivery unit 14. This system can provide either pulses oflight, or continuous scans of light, to the eye of a patient. The pulseduration, laser power density and the spot size on tissue all affect theexposure of the tissue to the treatment light (i.e. the dosage of lightfor the tissue), and thus characteristics of the lesions formed thereby.The control unit 10 controls the disposition (generation and delivery)of the light, and includes control electronics (i.e. a controller) 20and an input and output 22. Likewise, input from an input device 24(e.g. a joystick) and/or a graphic user interface (GUI) 26, may be usedby the control electronics 20 for controlling the light disposition.

In the light generation unit 12, a light beam 30 is generated by a lightsource 32, such as a 532 nm wavelength frequency-doubled, diode-pumpedsolid state laser. The beam 30 first encounters a mirror 34 which servesto monitor the light for safety purposes, reflecting a fixed portiontowards a photodiode 36 that measures its power. Following that, thelight beam 30 encounters a shutter 38, mirror 40, and minor 42. Shutter38 controls the delivery of the light beam 30. It may also be used togate the light, in addition to grossly blocking it. Minor 40 isconfigured as a turning minor as well as a combining minor to combineaiming light from a second light source 44 with light beam 30. Theaiming light is preferably aligned along the same path as the light beam30 to provide a visual indication of where the treatment light fromsource 32 will be projected onto the target tissue. After minor 42, thelight beam 30 (now including aiming light from source 44) is directedinto an optical fiber 46 via a lens 48. An optional minor 50 can be usedto direct a portion of the light beam to a second photodiode 52, whichserves purposes similar to those of minor 34 and photodiode 36, as wellas a redundant monitor of the state of shutter 38. Optical fiber 46 is aconvenient way to deliver the light from the light generation unit 12 tothe light delivery unit 14. However, free-space delivery of the lightmay be used instead, especially where the light generation and deliveryunits 12, 14 are integrally packaged together.

In the light delivery unit 14, lens 60 conditions the light exiting theoptical fiber 46. Lens 60 may be a single lens, or a compound lens. Ifit is a compound lens, lens 60 may be a zoom lens that adjusts the spotdiameter of the beam. This is useful for easy adjustment of the size ofpatterns and their elements on the target tissue as discussed furtherbelow. An additional lens 62 may be used to image the optical beamdownstream, and possibly act as a zoom lens, as shown. The image pointof lens 62 can be selected to minimize the size of optical elementsdownstream. A scanner 63, preferably having a pair of scanning optics(i.e. movable mirrors, wedges, and/or lenses), is used to deflect thebeam 30 to form a pattern P of spots or lines (straight or curved).Preferably, the scanning optics rotate or move in orthogonal X, Ydirections such that any desired pattern P can be produced. A lens 68focuses the beam onto a mirror 70 which redirects the beam through anophthalmic lens 72 and onto the target tissue. Mirror 70 can also bepart of a visualization apparatus which provides for visualization ofthe target tissue therethrough, either directly by the physician or by avisualization device 74. More specifically, visualization may beaccomplished by directly viewing the retina through minor 70, or bycapturing an image using a visualization device 74 (e.g. CCD camera) tobe displayed either on a remote monitor, or, as indicated by the dashedline of FIG. 1, on the graphical user interface 26.

Ideally, the lens 62 images the beam to a midpoint between scanningoptics 64, 66 and onto mirror 70. This may be done to minimize the sizeof the mirror 70 in an attempt to increase the overall solid anglesubtended by the visualization device 74. When minor 70 is small, it maybe placed directly in the visualization path without much disturbance.It may also be placed in the center of a binocular imaging apparatus,such as a slit lamp biomicroscope, without disturbing the visualization.Lens 62 could also be placed one focal length away from the opticalmidpoint of the scanning optics 64, 66 to produce a telecentric scan. Inthis case, mirror 70 would need to be large enough to contain the entirescan, and could be made a high reflector spectrally matched to theoutput of light sources 32, 44, and visualization accomplished bylooking through minor 70. To photopically balance the transmission ofmirror 70 (i.e. to make the colors of the tissue appear more natural), amore sophisticated optical coating can be used thereon instead of asimple green notch filter coating that produces pinkish images.

Ophthalmic lens 72 may be placed directly before the eye to aid invisualization, such as might be done with any ophthalmoscope, slitlampbiomicroscope, fundus camera, scanning laser ophthalmoscope (SLO), oroptical coherence tomography (OCT) system, which together with minor 70and optional ophthalmic lens 72 form the desired configuration for avisualization device for direct physician visualization. Ophthalmic lens72 may be a contact or non-contact lens, although a contact lens ispreferred because it serves the additional purpose of dampening any ofthe patient's eye movement.

The dosimetry pattern P of light formed by the scanning optics 64, 66can be a plurality of fixed spots, one or more continuous scansresulting in one or more straight or curved line segments, or acombination of both. Light sources 32, 44 and/or shutter 38 may be gatedon and off by commands from control electronics 20 via input and output22 to produce discrete spots, or simply run cw to create continuousscans as a means to produce dosimetry pattern P. Control electronics 20likewise can also be configured to control the position of mirror 70 andtherefore, ultimately, the dosimetry pattern P.

There are other techniques for creating dosimetry pattern P, such as bymoving the light source(s) directly. Alternately, scanner 63 cancomprise a two-dimensional acousto-optic deflector, or one or moreoptical elements with optical power that are translated. Mirror 70 maybe tilted or translated (if there is surface curvature) to either act asthe system scanner or augment beam movement already created by scanner63. In the case where mirror 70 has optical power, compensating opticalelements (not shown) may be required to produce an image, as opposed toa simple illumination. Similarly, the beam 30 could be divided usingpassive elements, such as diffractive optical elements (e.g. gratings orholograms), refractive elements (e.g. beam splitters, lenslet arrays,etc), or even active devices (e.g. adaptive optics) to create multiplebeams simultaneously. These beams could then be deployed at once forfaster treatment. They may also be used in conjunction with scanner 63to provide a mixed approach.

Thus, the above described system 1 is configured to produce a dosimetrypattern P (of fixed spots or a moving beam) with varying dosages oflight for different tissue areas within the dosimetry pattern P. Varyingdosage can be achieved by varying the time the beam dwells on any giventissue location (either varying the time a fixed spot is applied to aparticular tissue location, or varying the velocity a spot passing overa tissue location), varying the power density, and/or varying the spotsize of the beam. Therefore, any given location of the target tissuewill experience a dosage of light that depends upon the pulse duration,the power density, and the spot size of the light delivered to thatlocation. At least one of these “dosage parameters” are thus variedwithin the dosimetry pattern P to create lesions exhibiting differingvisual characteristics (e.g. size, color, darkness, etc.). Thus, theterm “pulse duration” is used herein to describe the duration ofexposure (i.e. the length of time light is applied to a given tissuelocation), including where the light beam is delivered to the targettissue without intentional motion for a particular time duration andwhere the light beam is made to move over the target tissue causing anexposure of a particular time duration. There are practical concerns,however, such as hand and eye movements that should be addressed toensure precise treatment is provided.

FIG. 2 shows an alternate embodiment of the system 1, which isparticularly suited for the treatment of the trabecular meshwork (TM).Here the ophthalmic contact lens of FIG. 1 is replaced with agonioscopic lens 80 with reflective side surfaces 82, which areoptimized for directing the light at an acute angle towards the TM.

Inherent flexibility of the scanned light beams enables many desiredclinical possibilities. Some or all of system 1 may be mounted directlyonto, among other things, an ophthalmic visualization tool such as aslit lamp biomicroscope, indirect ophthalmoscope, fundus camera,scanning laser ophthalmoscope, or optical coherence tomography system.Visualization device 74 may be employed to display the results ofdosimetry pattern P on the graphic user interface 26 for physicianreview and input. Alternately, system 1 itself may be configured toassess the resultant lesions directly by using visualization device 74,in order to create input for an inference algorithm or heuristic todetermine system settings for a given desired clinical result.Regardless of the degree of automation, such desired clinical resultsmay be the degree of lesion intensity (darkness) or color or size, orthe spatial selectivity of the treatment, and may be realized by varyingone or more dosage parameters (i.e. size, power density, and/or pulseduration) of the light beam.

Once the physician or the system 1 determines the desired treatmentconditions from the lesions generated by the delivery of the dosimetrypattern P onto the target tissue, system settings that dictate thedosage parameters of the beam at any given location (i.e. pulseduration, power density and/or spot size) can be set to produce thedesired clinical result during subsequent treatment. That subsequenttreatment can take the form of a single spot treatment, or a pattern Pof treatment light produced in a similar manner as the dosimetry patternP (i.e. a plurality of fixed spots, one or more continuous scansresulting in one or more straight or curved line segments, or acombination of both). It should be noted that the dosage parametersduring treatment can be set to produce clinical results that match or donot match one of the visible lesions produced by the delivery of thedosimetry pattern P. For example, if the desired clinical result is totreat tissue with light without producing a visible lesion, then thetreatment dosage parameters would be set to just below those thatproduced the lightest visible lesion from the dosimetry pattern P.

FIG. 3 shows an example of a dosimetry pattern P that is a linear arrayof fundamental spots 84 in which the pulse duration varies from spot tospot (e.g. progressively increasing from left to right), while the powerdensity remains constant. In this example, each of the spots results inthe formation of a visible or non-visible lesion. The first and secondspots of this exemplary five-spot dosimetry pattern P are shown withdotted outlines to illustrate that they did not produce visible lesions.Based upon observed character of the lesions, the physician or systemmay then choose treatment dosage parameters in a number of ways. First,treatment dosage parameters can be set to match those dosimetry patterndosage parameters that created one of the lesions exhibiting the desiredclinical result. This could also be as simple as the physician or systemidentifying the desirable lesion in the dosimetry pattern (e.g. via theGUI 26), and the system setting the treatment dosage parameters to matchthose dosimetry pattern dosage parameters that generated that lesion.Second, treatment dosage parameters can be set to match dosageparameters extrapolated from the dosimetry dosage parameters thatcreated one or more of the lesions of interest (e.g. dosage parametersin-between those that created two different lesions, or dosageparameters below those that generated the lightest lesion to generatenon-visible treatment lesions). Third, the physician or system cansimply identify the number of visible lesions generated by the dosimetrypattern. Based on this input, the system can determine the threshold ofdosage parameters needed to generate visible changes in tissue, andadjust the system dosage parameters to produce the desirable clinicalresult.

Because some spots 84 may not be visible, it is preferable (but notnecessary) to index the dosimetry pattern P starting from the end of thepattern formed by the highest dosimetry settings, which are those mostlikely to cause visible lesions. To minimize potential damage during thedosimetry test, it is preferably in many clinical applications to usepulse durations and power densities for dosimetry pattern P that areless than or equal to the expected therapeutic pulse, so that theapplied energy will be below the expected therapeutic energy. For betterstatistical predictability, dosimetry pattern P may include severalidentical rows, where an average result from the various rows are usedto determine the treatment dosage parameters.

FIG. 4 shows an alternate embodiment, where the dosimetry pattern P isformed by a single continuous scan of a light spot 84 to create a lineL. The velocity V of spot 84 varies along line L, causing the beam todwell on different tissue locations within dosimetry pattern P fordifferent amounts of time (i.e. varying the pulse duration on the tissueunderneath line L). Alternately, the power density and/or spot size canbe varied along line L, also resulting in a variable exposure along lineL. Similar to the example of FIG. 3, treatment results may be derivedfrom the position within dosimetry pattern P, in lieu of choosing adiscrete spot number with the desirable appearance or reporting thenumber of visible lesions. Thus, the patient's tissue response may bejudged, and the desired dosimetry prescribed empirically. The concurrentdisplay of the aiming light can facilitate this distinction.

Software, firmware and/or hardware in system 1 can include aphenomenological lookup table based on experimental measurements of theretinal coagulation at various laser power densities, pulse durationsand spot sizes. For example, once the dosimetry pattern P has beenapplied, and the number of visible legions resulting therefromidentified, the graphic user interface 26 can display an “expectedlesion” indicator 86, on an indicator bar 90, as shown in FIG. 5. Afurther input by the physician could be the position of a sliding bar 92along indicator bar 90 which represents the desired clinical result(e.g. the clinical degree of the lesion). The values 88 in this examplereflect the desired degree of the burn within the lesion: Light, Medium,and Intense. The values 94 under the bar may be extracted by thesoftware, firmware and/or hardware from a lookup table based on thelaser power density, spot size, pulse duration and the threshold oflesion visibility established by the dosimetry pattern scan.

FIG. 6 shows an alternate embodiment of indicator 86, where the systemincludes an inference engine. For example, after the application of atherapeutic pattern, the graphic user interface 26 displays an “observedlesion” slider bar 96 that is initially set to the same position as the“desired lesion” slider bar 92 of FIG. 5. When the lesions are not aspredicted by the results of dosimetry pattern P, the user could changethe “observed lesion” slider bar 96 to reflect the actual clinicalresult just produced by system 1. This would allow for the ongoingadjustment of the treatment dosage parameters without the need forutilizing further dosimetry patterns P. This automatic introduction ofexperimental data continuously to the database with physician feedbackregarding the actual results will help in building a larger and moreconfident lookup table. Of course, if the outcome of the therapy isobserved to be satisfactory, the physician can ignore the “observedlesion” control 86 and continue using the settings as they are.Furthermore, if the physician changes the spot size, the laser powerdensity and/or pulse duration, the position of bar slider 92 may beautomatically recalculated based on the model or a look-up table to keepthe lesions consistent. When visualization is integrated into the system1, and used as an input for system 1, this may be done during treatmentusing the same schemes previously discussed.

FIG. 7 shows a control/indicator 98 that simplifies the creation ofophthalmoscopically invisible lesions from the results of applying thedosimetry pattern P to target tissue. Control/indictor 98 consists of anindicator bar 90, similarly to that in FIG. 6. However, in this example,the degree of spatial selectivity is the value controlled. Experimentsby the inventors have shown the once the ophthalmoscopically visiblethreshold for creating a lesion is established, one may keep the powerdensity fixed, and decrease the pulse duration to better localize theextent of the lesion. Unexpectedly, animal models have shown that thiscan be as straightforward as adjusting power density to achieve avisible burn at 20 ms, and then reducing the pulse duration to 5 ms inorder to produce lesions whose axial extent is confined to the RPE andphotoreceptor outer-segments. Once the lesion threshold is identified byapplying the dosimetry pattern P, the axial extent of the lesion can beselected by reducing the pulse duration. The relationship between pulseduration and the extent of thermal damage is not linear. The use ofcontrol 98 simplifies operation by providing the user an efficient meansby which to select the spatial selectivity (or, axial extent of thelesion) by moving a slider bar 92 in a manner similar to that describedfor FIG. 5. Here, however, the values 100 and parameters 102 reflect thespatial selectivity and the pulse duration, respectively. Spatialselectivity has been denoted by the terms High (H), Medium (M), and Low(L). High selectivity lesions are more confined than low selectivitylesions.

FIG. 8 shows the use of a mixture of ophthalmoscopically visible andinvisible lesions to produce patterns that are easy to place adjacent toeach other. A therapeutic pattern 104 may include various lesionscorresponding to ophthalmoscopically invisible lesions 106 (dashedoutlines) to perform minimally traumatic therapy, and visible lesions108 (solid outlines) at the periphery of the pattern for producingfiducial marks to align the next pattern. These visible lesions 108 maybe of longer pulse duration and/or higher power density, thanophthalmoscopically invisible lesions 106, for example. These fiducialmarks will allow for the precise placement of adjacent patterns withoutcausing large amounts of otherwise undue damage. Of course, otherconfigurations and arrangements of fiducial marks are possible. By firstdetermining the threshold of dosage parameters needed to generatevisible changes in tissue via the application of the dosimetry pattern Pas described above with reference to FIG. 3, the system dosageparameters necessary to generate visible lesions 108 can be determined.

It is to be understood that the present invention is not limited to theembodiment(s) described above and illustrated herein, but encompassesany and all variations falling within the scope of the appended claims.For example, while the preferred light sources for generating thedosimetry pattern P and the treatment beam/pattern are lasers, anyappropriate light source can be used to generate the light beams fordosimetry pattern P and the treatment beam/pattern. The functionality ofcontrol electronics 20 can be hardware only, and/or includefunctionality found by software and/or firmware running thereon as well.

1-11. (canceled)
 12. A system for treating ophthalmic target tissueusing a treatment pattern of lesions, wherein the treatment patterncomprises a first sub-pattern of lesions and a second sub-pattern oflesions, the system comprising: a light source for generating a beam oflight towards a beam delivery unit; the beam delivery unit configured todeliver the beam of light to the ophthalmic target tissue, the beamdelivery unit including a scanner unit configured to deflect the beam oflight; and a control unit operatively coupled to and configured tocontrol at least one of the light source and the beam delivery unit to:deliver the beam of light to the ophthalmic target tissue, wherein thedelivery creates a first sub-pattern of lesions on the ophthalmic targettissue, the first sub-pattern including: a plurality ofophthalmoscopically invisible lesions, and at least oneophthalmoscopically visible lesion; and a visualization deviceconfigured to identify an ophthalmoscopically visible lesion from thefirst sub-pattern of lesions, wherein the control unit is furtherconfigured to control a least one of the light source and the beamdelivery unit to: after creating the first sub-pattern, align the beamof light based on the identified ophthalmoscopically visible lesion fromthe first sub-pattern, and create the second sub-pattern of lesions onthe ophthalmic target tissue using the aligned beam of light, whereinthe ophthalmoscopically visible lesion from the first sub-patternindicates an end of the first sub-pattern, and wherein the secondsub-pattern is adjacent the first sub-pattern but does not overlap thefirst sub-pattern.
 13. The system of claim 12, wherein the control unitis further configured to adjust the pulse duration of the beam of light,and wherein the plurality of ophthalmoscopically invisible lesions areformed using a shorter pulse duration of the beam of light than the atleast one ophthalmoscopically visible lesion.
 14. The system of claim12, wherein the control unit is further configured to adjust the powerdensity of the beam of light, and wherein the plurality ofophthalmoscopically invisible lesions are formed using a lower powerdensity of the beam of light than the at least one ophthalmoscopicallyvisible lesion.
 15. The system of claim 12, wherein the control unit isfurther configured to adjust the pulse duration and the power density ofthe beam of light, and wherein the plurality of ophthalmoscopicallyinvisible lesions are formed using a shorter pulse duration and a lowerpower density of the beam of light than the at least oneophthalmoscopically visible lesion.
 16. The system of claim 12, wherein:the first sub-pattern includes a first row of lesions.
 17. The system ofclaim 13, wherein: the ophthalmoscopically visible lesion from the firstsub-pattern that indicates an end of the first sub-pattern is the firstlesion in the first row of lesions.
 18. The system of claim 13, whereinthe first sub-pattern includes at least two rows of lesions, wherein afirst row of the at least two rows of lesions is aligned above a secondrow of the at least two rows of lesions, wherein the ophthalmoscopicallyvisible lesion from the first sub-pattern that indicates an end of thefirst sub-pattern is at one end of the second row of lesions.